RESUMEN
STUDY OBJECTIVE: To investigate whether carbon dioxide pneumoperitoneum causes ischemia-reperfusion injury to the ovaries during laparoscopic surgery. DESIGN: A prospective controlled clinical study (Canadian Task Force classification II-1). SETTING: A tertiary academic center. PATIENTS: Premenopausal women who underwent hysterectomy with bilateral salpingo-oophorectomy (HSO) via open abdominal and laparoscopic approaches between 2014 and 2015. INTERVENTIONS: In both surgical approaches, unilateral oophorectomy was performed immediately after abdominal entry, and the remaining contralateral ovary was excised at the end of the hysterectomy in order to compare the effect of these surgical procedures on ovarian tissue. Additionally, plasma samples were collected at the following time points: (1) before abdominal entry, (2) at the end of hysterectomy, and (3) before contralateral oophorectomy. Plasma samples were assessed for biochemical oxidative stress markers malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Ovarian tissue samples were assessed for MDA and further evaluated for ischemia-reperfusion injury using a histologic scoring method. MEASUREMENTS AND MAIN RESULTS: Twenty premenopausal women undergoing HSO via open abdominal surgery (n = 10) and laparoscopy (n = 10) were included. Baseline characteristics (age, body mass index, parity, and gravida) and operative data (operative time, estimated blood loss, and intraoperative complication) were similar between groups. Perioperative plasma MDA levels, histologic scores, and tissue oxidative stress markers did not show a significant difference in either group or between groups. However, plasma 8-OHdG levels were significantly different when the second sample in the abdominal HSO group was compared with the first sample in the abdominal HSO group and the third sample in the laparoscopic HSO group (p = .012 and .001, respectively). CONCLUSION: Carbon dioxide pneumoperitoneum does not cause ischemia-reperfusion injury in the human ovaries at clinically safe levels of intra-abdominal pressure.
Asunto(s)
Dióxido de Carbono , Laparoscopía , Ovario/irrigación sanguínea , Neumoperitoneo Artificial , Daño por Reperfusión , 8-Hidroxi-2'-Desoxicoguanosina , Desoxiguanosina/análogos & derivados , Desoxiguanosina/sangre , Femenino , Humanos , Histerectomía/métodos , Insuflación , Malondialdehído/sangre , Persona de Mediana Edad , Ovariectomía , Estudios ProspectivosRESUMEN
Pancreatic ductal adenocarcinoma (PDAC) is considered one of the deadliest human cancers, with 1-5% 5-year survival rates (~6-month median survival duration) despite therapy; thus, PDAC represents an unmet therapeutic challenge. PDAC is the major histological subtype, comprising 90% of all pancreatic cancers. It is a highly complex and aggressive malignancy, presenting with early local invasion and metastasis, and is resistant to most therapies, all of which are believed to contribute to its extremely poor prognosis. PDAC is characterized by molecular alterations, including mutations of K-RAS (~90% of cases), TP53, transforming growth factor-ß, Hedgehog, WNT and NOTCH signaling pathways. Given that cancer stem cells have a crucial role not only in tumor initiation and progression, but also in drug resistance and relapse or recurrence of various cancer types, they may be excellent targets for effective novel therapeutic approaches. Here, we reviewed recent therapeutic strategies targeting pancreatic cancer stem cells using chemotherapeutics and targeted drugs, non-coding RNAs (i.e., siRNA and miRNAs), immunotherapy, and natural compounds.
Asunto(s)
Células Madre Neoplásicas , Neoplasias Pancreáticas/terapia , Animales , Dieta , Humanos , Inmunoterapia , MicroARNs , Células Madre Neoplásicas/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Transducción de SeñalRESUMEN
Immunotherapy is a promising field that offers alternative methods for treatment of cancer. The current strategy consists of cancer vaccines, monoclonal antibodies, and cellular therapies. Cancer vaccines aim to eradicate cancer cells via immune system. Thus, they may attack these cells derived from any type of cancer, besides their role in preventing cancer. Lymphocytes and dendritic cells are often used in cellular therapy. In addition, monoclonal antibodies are designed to target specific antigens found in cancer cells. Currently, at least 12 clinically approved monoclonal antibodies are being used and many cancer vaccines are being developed with ongoing phase studies for cancer therapy. Relevant studies are focused on glioma and several other cancer types. Correspondingly, the combination of effective methods may enhance the efficacy of immunotherapy. It is thought that particularly immune checkpoint inhibitors will play a crucial role in immunotherapeutic approaches.